romiplostim in treating hepatitis c-infected patients with thrombocytopenia

Conditions: Hepatitis C Infection; Thrombocytopenia

Summary: rationale: romiplostim may cause the body to make platelets. purpose: this randomized phase ii trial is studying how well romiplostim works in treating hepatitis c-infected patients with thrombocytopenia.

primary objectives: i. to assess the platelet count response to administration of weekly romiplostim patients with hcv infection whose initial platelet count is \< 70,000/l. secondary objectives: i. to assess the safety and tolerability of romiplostim the treatment of patients with hcv infection and thrombocytopenia; including physical symptoms and findings, hematologic, serum chemistries and liver function tests and adverse events. ii. to assess the ability of romiplostim to enable subjects to achieve a platelet count sufficient to start antiviral therapy. iii. to assess the ability of romiplostim to maintain platelet counts greater than 50,000/l while receiving antiviral therapy with pegylated interferon and ribavirin. outline: patients are randomized to 1 of 2 treatment arms. arm i: patients receive romiplostim subcutaneously once weekly for 8 weeks in the absence of disease progression or unacceptable toxicity. arm ii: patients receive placebo subcutaneously once weekly for 8 weeks. patients failing to achieve a platelet count of \> 100,000/l cross over to arm i. patients achieving a platelet count of \> 100,000/l at 8 weeks receive peg-interferon alfa-2a subcutaneously once weekly and oral ribavirin once daily. treatment repeats every 7 days for 24-48 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed at 4 and 36 weeks.

Eligibility criteria:
inclusion * all patients with hcv virus infection documented by detectable plasma hcv antibodies and rna who would be excluded by fda criteria for antiviral treatment with peginterferon-alpha 2a and ribavirin due to thrombocytopenia (platelets \< 70,000/l); patients cannot have received previous anti-viral therapy with interferon/ribavirin * liver biopsy indicating chronic hepatitis within the previous 2 years * mean platelet count of \ = 75,000/l * neutrophil count of \>= 1000/mcl * hemoglobin \>= 11gm/dl and no evidence of active bleeding * prothrombin time (pt) inr \< 1.6 seconds * albumin \>= 2.5 gm/dl * alt \>= 1.2 and \< 10 times upper limit of normal * no evidence of either ischemic change or cardiac injury on 12-lead electrocardiogram (ekg) * negative pregnancy test and women must be using adequate contraception for at least 2 weeks prior to enrollment and while enrolled in the study * signed informed consent within 2 weeks of enrollment and randomization exclusion * received previous anti-viral therapy with interferon/ribavirin * child's class b and c or acute decompensated liver disease * human immunodeficiency virus (hiv) infection or co-infected with hepatitis b virus * any untreated active infection * active malignancy, known primary bone marrow disorder (myelodysplasia, myeloproliferative disease, etc.), or history of blood or bone marrow transplantation; patients with documented hemoglobinopathies * active vasculitis associated with cryoglobulinemia as manifested by either renal disease or dermatologic findings * positive pregnancy test or men with pregnant partners * creatinine and bun of greater than twice (2x) the upper limits of normal * history of venous or arterial thrombosis, myocardial infarction or thrombotic stroke * patients who in the investigators opinion will fail to be compliant or have other contraindication to treatment on this study * other inherited or acquired liver disease * previous solid organ transplant * known hypersensitivity to e. coli derived recombinant proteins * active rheumatologic disease including systemic lupus erythematosis * known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura